Antagonism to muscarinic receptors are known to cause bronchodilation, gastrointestinal hypanakinetics, gastric hyposecretion, dry mouth, mydriasis, suppression of bladder contraction, hypohidrosis, tachycardia and the like "Basic and Clinical Pharmacology", 4th ed., APPLETON & RANGE, pp. 83-92 (1989); Drug News & Perspective, 5(6), pp. 345-352 (1992)!.
It has been made clear through recent studies that there are at least three subtypes of muscarinic receptors; the M.sub.1 receptors being present mainly in the brain, the M.sub.2 receptors mainly in the heart, and the M.sub.3 receptors, on smooth muscles and glandular tissues. Whereas, all of the large number of compounds heretofore known to exhibit antagonism to muscarinic receptors non-selectively antagonize the three subtypes of muscarinic receptors. Consequently, attempts to use these compounds as therapeutic or prophylactic agents for diseases of the respiratory system have caused undesirable side effects such as dry mouth, nausea and mydriasis. Still in addition, particularly serious side effects associated with the central nervous system, such as dementia, attributable to the M.sub.1 receptors and those associated with the heart, such as tachycardia mediated by the M.sub.2 receptors pose problems and their solution is strongly demanded.
We have disclosed, as a drug meeting the demand, 1,4-disubstituted piperidine derivatives (see: PCT WO96/33973). However, creation of even more excellent drug has been in demand.
An object of the present invention is to create even a better drug than said known compounds, whereby to provide pharmaceutics exhibiting highly selective antagonism to M.sub.3 receptors and minimizing adverse side effect and which, therefore, provide safe and effective pharmaceutics for treatment or prophylaxis of diseases associated with muscarine M.sub.3 receptors, e.g., such respiratory diseases as chronic obstructive pulmonary diseases, chronic bronchitis, asthma and rhinitis; digestive diseases such as irritable bowel syndrome, convulsive colitis, diverticulitis and pain accompanying contraction of smooth muscles of the digestive system; urinary disorders like urinary incontinence and frequency in neurologic pollakiurea, neurologic bladder, nocturnal enuresis, unstable bladder, cystospasm and chronic cystisis; and motion sickness.